TCR antigen-induced cell death occurs from a late G1 phase cell cycle check point.
Deletion of antigen-activated T cells after an immune response and during peripheral negative selection after strong T cell receptor (TCR) engagement of cycling T cells occurs by an apoptotic process termed TCR antigen-induced cell death (AID). By analyzing the timing of death, cell cycle markers, BrdU-labeled S phase cells, and phase-specific centrifugally elutriated cultures from stimulated Jurkat T cells and peripheral blood lymphocytes, we found that AID occurs from a late G1 check point prior to activation of cyclin E:Cdk2 complexes. T cells stimulated to undergo AID can be rescued by effecting an early G1 block by direct transduction of p16INK4a tumor suppressor protein or by inactivation of the retinoblastoma tumor suppressor protein (pRb) by transduced HPV E7 protein. These results suggest that AID occurs from a late G1 death check point in a pRb-dependent fashion.
Lissy
N A
NA
Howard Hughes Medical Institute, Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Van Dyk
L F
LF
Becker-Hapak
M
M
Vocero-Akbani
A
A
Mendler
J H
JH
Dowdy
S F
SF
D017209:Apoptosis / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D004789:Enzyme Activation; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D008213:Lymphocyte Activation / Q000502:physiology; D008214:Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure*; D010766:Phosphorylation; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D016196:S Phase / Q000502:physiology; D012680:Sensitivity and Specificity
D011948:Receptors, Antigen, T-Cell; D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases